GEN Exclusives

American Gut Project Wants Your Stool

The microbiome study is collecting samples from humans and animals alike.

As of November 11, American Gut sequenced microbes within 2,102 samples from 1,589 participants. [Sebastian Kaulitzki-Fotolia.com]

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Antoni van Leeuwenhoek offered the first description of the intestinal protozoa or “animalcules” he discovered in 1681: “I have generally seen, in my excrement, many irregular particles of sundry sizes, most of them tending to a round figure, which are very clear and of a yellow colour [sic],” the “Father of Microbiology” told the Royal Society.

More than three centuries later, 53 researchers representing a mix of professors, grad students, postdocs, and technicians are working on a far more sophisticated picture of the fecal, oral, and skin bacterial communities along the length of the human gut.

The American Gut Project is a crowdfunded research project run by the lab of Rob Knight, Ph.D., of the University of Colorado, Boulder. Dr. Knight, a Howard Hughes Medical Institute Early Career Scientist whose lab is part of the BioFrontiers Institute at the University of Colorado, launched the project with Jeff Leach, founder of the Human Food Project, which studies modern disease in the context of the ancient microbial world.

As of November 11, American Gut sequenced microbes within 2,102 samples from 1,589 participants, of which 892 samples have been deposited in the European Nucleotide Archive and are public domain. Earlier this month, the project released its first individualized data to participants, who cannot be convicted felons or younger than three months old.

Virtually anyone else can take part, and American Gut remains open to new participants, who have agreed to provide samples from themselves or their pets. A research team led by Dr. Knight earlier this year published study results in eLife based on a study of fecal, skin, and oral microbiota from 60 families. Results showed that household members, especially couples, shared more microbiota than people from different households, while dog ownership significantly increased shared-skin microbiota in cohabiting adults.

“At this point, we’re beginning to see some suggested patterns, but we’re not in position to say anything strong about any possible correlations,” Daniel McDonald, a doctoral student in Dr. Knight’s lab who is on American Gut’s core research team, told GEN. “We still actually have fairly small sample sizes for some of the interesting categories we would like to study.”

Diet, Antibiotics, and the Microbiome

One area the project is studying is diet—what if any differences in gut bacteria can be seen in people with paleo diets vs. the typical omnivore? Preliminary results released in September showed that younger people, especially babies, had more protobacteria, as was expected from past published results; while vegetarians and vegans had fewer protobacteria, which have been linked to inflammation. Also showing fewer protobacteria were paleo dieters, though their results showed they had more firmicutes, which have been linked to obesity.

Preliminary results also showed that the fecal, oral, and skin bacteria fell into distinct areas that could be mapped as three points of a triangle, very similarly to the data collected by three studies involving far smaller populations: The Global Gut Project (531 total participants), Human Microbiome Project (242), and the Personal Genome Project (86)—whose founder George Church of Harvard Medical School is involved with American Gut.

“We have a reasonable idea about the microbiome of a human being. We have some understanding of microbiomes of mice, though typically it’s lab mice, and not wild-type mice. We have some understanding of the microbiome of rats and dogs. We have a little bit of an understanding of the microbiome of the common house fly and termites, and some types of fish,” McDonald said. “We really don’t understand the types of organisms that live on and inside most animals, all organisms on the planet. Beginning to expand that knowledge out will be very beneficial to a wide range of studies.

A handful of notable participants have agreed to share their results, including author Michael Pollan, ultramarathon runner Dean Karnazes, and Shannon Ford, an advocate for the Paleo diet and Mrs. United States 2011. Pollan contributed three samples—one taken before he went on antibiotics for a dental procedure, another taken a week following antibiotics, and a third about three months later, and closer in results to the first sample.

“We definitely see some evidence—and this is not too surprising—that antibiotics do have some type of lasting effect, at least for weeks to months, before a microbiome is able to recover,” McDonald said. “We’re also seeing some trends associated with diet, which again is not entirely too surprising yet. But what we’re hoping is, as we increase the sample size, we’ll begin to identify the actual driving factors in those differences, and we can begin to hopefully find the commonalities that are present.”

Not Everyone Trusts the Gut

American Gut leaders emphasize that results from its sample studies constitute basic research rather than any medical diagnosis. But studies of possible medical applications are under way. The Knight lab is using funding from the Crohn’s and Colitis Foundation to explore if, given just a fecal sample, researchers can determine if someone has Crohn’s disease, and what type. The lab is also collaborating with Paul Wischmeyer, M.D., of Anschutz Medical Center at University of Colorado, Denver, to perform an initial characterization of the effects of ICU stays on the microbiome.

By stressing that data collected is not medically actionable, American Gut sounds more like the direct-to-consumer testing carried out by some companies than bona fide research, Jeremy Gruber, J.D., president and executive director of the Council for Responsible Genetics, told GEN.

So too, Gruber said, does the fact American Gut charges participants for taking part, starting at $99. For $129, participants can fund two kits, the second for someone in Africa, South America or Asia. The priciest option or “perk” at $25,000 pays for “ultra-deep” sequencing—details are undisclosed pending future publication—of a microbiome sample, aimed at generating as many individual bacterial genomes as possible.

“They’re not offering back your data alone. They’re offering back an interpretation. And any time there’s an interpretation of medical data, or medically related data, there should be some oversight to ensure that it’s factually correct, that it’s put in proper context, that the individual truly understands what they’re receiving. It’s not entirely clear that’s the case here,” Gruber said.

Gruber added that the collection of a significant amount of personal information “raises concerns regarding what exactly are the privacy protections that are in place, to make sure that what is being promised actually occurs, what processes are being used to de-identify the information, and what is being told to the consumer to encourage them to participate in the project.” Genetic data, he added, should be protected as strongly as personal medical records and Social Security numbers.

Many of Gruber’s arguments mirror those asserted in an NPR report by three other bioethicists— Hank Greely of Stanford University; Pilar Ossorio of the University of Wisconsin, Madison; and Eric Juengst of University of North Carolina, Chapel Hill. They questioned how participants’ data can be kept confidential, whether their DNA might inadvertently go public, who owns the data, and why children’s data are being collected.

In response, American Gut’s leaders issued a statement noting that every aspect of the project is voluntary, that no human DNA will be sequenced from samples, that any DNA sequenced from pricier perks will be removed as in the Human Microbiome Project, that project data is free and owned by no one, and that data will remain confidential under protocols approved and monitored by CU’s Institutional Review Board.

“These protocols assure the data are safely collected and properly de-identified, and that identifying information is stored in a confidential manner—in this case, on access-controlled servers sitting in a university-run data center that is monitored 24/7 and which requires keycard access,” Dr. Knight, McDonald, and Leach said in a statement. “We do appreciate that no project can ensure privacy 100%, but we are making every effort to do this, which involves considerable extra effort.”

As for seeking payment from participants, McDonald told GEN American Gut lacks the funding to pay participants: “I would absolutely love to be in a position where we could offer some type of monetary compensation for participation in the project. But it is simply not feasible for the American Gut at this point,” McDonald said.

As of November 11, the project raised $615,450 in donations from more than 6,700 people and four companies that supported individuals seeking to participate but unable to give toward American Gut. That’s one indication that there’s public interest in the project. Not to mention the 18,000 people who initially requested more information last year. The project hopes to collect samples from 20,000 people.

The best way to reach that goal, and go beyond, is by communicating clearly how participants’ data will be protected—and working toward lowering the cost through additional foundation funding; McDonald said NIH funding was unlikely given the dearth of exclusion criteria, though years of flat budgets aren’t encouraging. The additional funding could support the longer-range medical research needed to translate the raw data of American Gut into more usable knowledge that benefits participants, from improving their diet to treating their disease.

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